The ability to detect, identify, and quantify trace quantities of analytes has become increasingly important in virtually every scientific discipline, ranging from part per billion analyses of pollutants in sub-surface water to analysis of cancer treatment drugs in blood serum. Raman spectroscopy is one analytical technique that provides rich optical-spectral information, and surface-enhanced Raman spectroscopy (SERS) has proven to be one of the most sensitive methods for performing quantitative and qualitative analyses. A Raman spectrum, similar to an infrared spectrum, consists of a wavelength distribution of bands corresponding to molecular vibrations specific to the sample being analyzed (the analyte). In the practice of Raman spectroscopy, the beam from a light source, generally a laser, is focused upon (impinged upon) a sample (solid or solution) to thereby generate inelastically scattered radiation, which is then optically collected and directed into a wavelength-dispersive spectrometer in which a detector converts the energy of impinging photons to electrical signal intensity.
Among many analytical techniques that can be used for chemical structure analysis, Raman spectroscopy is attractive because of its capability to provide rich structure information from a small optically-focused area or detection cavity, such as one or more a small sample containers (“wells”) located in a sample plate. Compared to a fluorescent spectrum that normally has a single peak with half peak width of tens of nanometers to hundreds of nanometers, a Raman spectrum has multiple bonding-structure-related peaks with half peak width of as small as a few nanometers.
Currently, most commercial Raman instruments are designed to analyze solid samples. High-throughput type instruments (i.e., multiple samples per run) use non-confocal excitation/detection, while samples requiring higher laser excitation and analyte detection sensitivity usually are analyzed in a single sample per run. Confocal based Raman instruments, compared to non-confocal, are difficult to automate due to inconsistencies in automated focusing. Also, Raman signals are generated by measuring light reflectivity from the samples. Because a certain amount of laser light is lost due to scattering and other causes, useful signal intensity is lost.
With surface-enhanced Raman scattering detection (SERS), sensitivity of detection is much improved due to the chemical and electronic effects of high surface area materials interacting with analyte but, still, current commercial products and systems are not yet optimized for SERS analysis.
In solution-based samples of SERS active particles or standard Raman samples, a reflective sample container (well) would increase the laser excitation signal intensity impinging on the sample, and an engineered reflective surface could better direct the resulting Raman signal intensity into the collection optics and the path of the detection for improved signal intensity.